Fibrin sealants, also known as fibrin glues, have been in use for decades (see, for example, Tabélé, et al. Organic Glues or Fibrin Glues from Pooled Plasma: Efficacy, Safety and Potential as Scaffold Delivery Systems. J Pharm Pharmaceut Sci 2012, 15:124-140; Dickneite, G et al. A comparison of fibrin sealants in relation to their in vitro and in vivo properties. Thrombosis Res 2003, 112:73-82).
Oftentimes, fibrin sealants consist of two components, a fibrinogen comprising component and a thrombin comprising component, that are delivered to a target area separately by using a double-barreled delivery device, e.g., as described in U.S. Pat. No. 4,874,368, 4,978,336, 5,104,375, 6,234,994 and EP-B-0 037 393, PCT Patent Application WO2007059801, U.S. Pat. Nos. 6,613,020, and 6,783,514.
Typically, a fibrin sealant clot is formed by enzymatic reactions involving fibrinogen, thrombin and Factor XIII. The thrombin converts the fibrinogen to fibrin by an enzymatic action at a rate determined by the concentration of thrombin. Factor XIII, an enzyme of the blood coagulation system, cross-links and stabilizes the fibrin clot. This process bypasses most of the steps of normal coagulation and mimics its last phase.
Some manufacturers add anti-proteolytic agents to the fibrin glue formulation (e.g. as described in PCT Patent Application WO93/05822) or specifically remove the plasminogen in order to stop or delay fibrinolysis (e.g. as described in U.S. Pat. Nos. 5,792,835 and 7,125,569). The thrombin component comprises the enzyme thrombin, which can be from human or animal (e.g. bovine or porcine) origin or produced by recombinant technology. The fibrinogen component comprises the thrombin substrate, fibrinogen, which can be from human or animal (e.g. bovine or porcine) origin or produced by recombinant technology. Upon mixing the two components, thrombin cleaves fibrinogen thus allowing the latter to polymerize into fibrin and produce the sealant.
In prior art devices, two supply reservoirs, each containing one adhesive/sealant component, are held together by a holding device which makes it possible to hold the application device between the fingers of a hand and to operate the device by one hand.
A prior art device referred to herein as a “multi-component” device may include multiple syringes e.g. two syringes. For example, the fibrinogen component within a first syringe comprises Factor XIII and fibrinogen, and the thrombin component within a second syringe e.g. as described in U.S. Pat. No. 4,978,336. Typically, the plungers of the first and second syringes are simultaneously engaged e.g. by a coupling element and motion of the coupling element in a dispensing direction causes each engaged plunger to longitudinally slide within its respective syringe barrel so that the plungers are depressed at the same time and speed. Mixture of the two components results in a spontaneous formation of a fibrin clot, which may be used as a surgical glue.
When referring to a “multi-component” device, the term “component” refers to a protein mixture contained within a reservoir e.g. a syringe. Thus, “multi-component” device require multiple reservoirs where a different protein mixture is respectively present within each reservoir.
Oftentimes, prior art devices also include an application tip installed on the dispensing end of the device where respective outflows from the syringes are mixed. After leaving the syringes, the outflows are maintained separate from each other, and are only mixed at the exit of the tip. Nevertheless, because the two components immediately form a clot when mixed together, maintaining a steady outflow of liquid from the device is critical, to prevent the tip from getting blocked.